title: Prostaglandin reductase-3 negatively modulates adipogenesis through regulation of PPARγ activity.
abstract: Adipocyte differentiation is a multistep program under regulation by several factors. Peroxisome proliferator-activated receptor γ (PPARγ) serves as a master regulator of adipogenesis. However, the endogenous ligand for PPARγ remained elusive until 15-keto-PGE2 was identified recently as an endogenous PPARγ ligand. In this study, we demonstrate that zinc-containing alcohol dehydrogenase 2 (ZADH2; here termed prostaglandin reductase-3, PTGR-3) is a new member of prostaglandin reductase family that converts 15-keto-PGE2 to 13,14-dihydro-15-keto-PGE2. Adipogenesis is accelerated when endogenous PTGR-3 is silenced in 3T3-L1 preadipocytes, whereas forced expression of PTGR-3 significantly decreases adipogenesis. PTGR-3 expression decreased during adipocyte differentiation, accompanied by an increased level of 15-keto-PGE2. 15-keto-PGE2 exerts a potent proadipogenic effect by enhancing PPARγ activity, whereas overexpression of PTGR-3 in 3T3-L1 preadipocytes markedly suppressed the proadipogenic effect of 15-keto-PGE2 by repressing PPARγ activity. Taken together, these findings demonstrate for the first time that PTGR-3 is a novel 15-oxoprostaglandin-Δ(13)-reductase and plays a critical role in modulation of normal adipocyte differentiation via regulation of PPARγ activity. Thus, modulation of PTGR-3 might provide a novel avenue for treating obesity and related metabolic disorders.
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan.
authors.forename: Yu-Hsiang
authors.initials: YH
authors.lastname: Yu
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Chang
authors.forename: Tseng-Hsiung
authors.initials: TH
authors.lastname: Su
authors.forename: Jiun-Yi
authors.initials: JY
authors.lastname: Nong
authors.forename: Chao-Chin
authors.initials: CC
authors.lastname: Li
authors.forename: Lee-Ming
authors.initials: LM
authors.lastname: Chuang
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000201:enzymology / Q000473:pathology; D050156:Adipogenesis; D052436:Adipose Tissue, White / Q000166:cytology / Q000201:enzymology / Q000473:pathology; D050154:Adiposity; D000818:Animals; D002460:Cell Line; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000378:metabolism; D051379:Mice; D009765:Obesity / Q000201:enzymology / Q000473:pathology; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*
chemical_list: D047495:PPAR gamma; C026346:15-ketoprostaglandin E2; C025087:15-keto-13,14-dihydroprostaglandin E2; D044925:Oxidoreductases Acting on CH-CH Group Donors; C587909:prostaglandin reductase-3, mouse; D015232:Dinoprostone
keywords: adipocyte differentiation; eicosanoid; ligand; nuclear receptor